The overall objective of the proposed research is to provide a more clear understanding of the mechanisms by which cell proliferation is regulated. We have found that polyamine synthesis, which is closely related to growth in all biological systems studied, is stimulated in cultured animal cells by a non-dialyzable component of serum. It has also been found that certain protease inhibitors, which we have shown to cause a reversible cessation of growth in vitro, rapidly decrease the synthesis of polyamines. We are attempting to purify the serum factor and to investigate the mechanisms by which polyamine synthesis is regulated in cultured cells. The role of proteases in this mechanism as well as in the stimulation of growth is also under study.